Entrada Therapeutics (Nasdaq: TRDA) reported early clinical data for its exon 44-skipping program ENTR-601-44 in Duchenne muscular dystrophy (DMD), with results from a small, placebo-controlled cohort indicating a modest increase in dystrophin and an exploratory functional signal that requires confirmation in larger studies. The findings position the asset within the exon-skipping class, where delivery and magnitude of dystrophin restoration remain key variables.
The Boston-based Entrada reported topline results from Cohort 1 of the Phase I/II ELEVATE-44-201 study evaluating ENTR-601-44 in ambulatory pediatric patients with Duchenne muscular dystrophy amenable to exon 44 skipping. The double-blind, placebo-controlled cohort enrolled eight participants aged six to 17, randomized 3:1 to receive three intravenous doses of ENTR-601-44 at 6 mg/kg or placebo. The study met its primary objective on safety and tolerability, with all treatment-emergent adverse events reported as mild to moderate and no serious adverse events or discontinuations.
Muscle biopsy data showed a mean increase in dystrophin of 2.36% over a baseline of 4.00%, alongside a 2.31% increase in exon skipping from a 2.66% baseline. Functional assessment using Time to Rise velocity showed an improvement in the treatment group, with a mean difference versus placebo of 0.115 (p<0.05) in a post hoc analysis. The study was not powered for efficacy, and the functional endpoint was not a prespecified primary outcome, limiting interpretation of the observed signal. Plasma exposure in treated participants was lower than levels previously observed in healthy adult volunteers, with the company indicating that higher exposure and dystrophin levels are predicted at the 12 mg/kg dose being evaluated in Cohort 2.
The ELEVATE-44-201 trial is a global, randomized, double-blind, placebo-controlled Phase I/II study enrolling ambulatory patients aged four to 20 across sites in the UK and EU. Cohort 1 represents a small subset of the planned study population, and all participants have transitioned to the open-label portion, where they will continue receiving ENTR-601-44. Additional cohorts at higher dose levels are ongoing, with data expected in 2026.